Our research aims will focus on studying the functional properties of human hemoglobins which have been specifically altered either by chemical modification or by natural genetic mutation. Such hemoglobins will be compared to normal human hemoglobin A in order to get more precise structural-functional correlates. This general approach will be used in the study of hemoglobin S and sickling phenomenon. By this means we hope to gain information on the sites on the sickle hemoglobin molecule which are responsible for the aggregation of its deoxy conformation into microfilaments or tactoids. We will attempt to prepare chemically modified forms of hemoglobin S in which sickling is inhibited with minimal disturbance of the molecule's functional properties; i.e., oxygen binding and heme-heme interaction. Methodological approach will include the preparation and isolation of the chemically modified or mutant hemoglobins, followed by the study of their functional properties. Emphasis will be placed on oxygen binding equilbria of these hemoglobins, their Bohr effect, and their interaction with organic phosphates. Sickling phenomenon will be studied by the measurement of minimum concentration for gelation and viscosity.